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Lysosomal Disorders

Oncology

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Authors

This study compared the activity and toxicity of fluorouracil (5-FU)/cisplatin with the combination tegafur and uracil (UFT)/cisplatin in the neoadjuvant treatment of locally advanced-stage III or IV (M0)-head and neck

Neoadjuvant Therapy With Cisplatin/Fluorouracil vs  Cisplatin/UFT in Locally Advanced Squamous Cell Head  and Neck Cancer

Patient use of the 2 FDA-approved gene therapy products for sickle cell disease (SCD), Vertex Pharmaceuticals' and CRISPR Therapeutics’ 

 (exa-cel; marketed as Casgevy) and bluebird bio’s 

 (lovo-cel; marketed as Lyfgenia), in the commercial setting has remained low.

Despite the approval of both gene therapy products by the FDA occurring simultaneously on December 8, 2023, only 4 patients have begun treatment with lovo-cel in the commercial setting, while 20 patients are reported to have begun treatment with exa-cel. Alongside the number for lovo-cel, bluebird also pointed out that this year 4 patients have started on elivaldogene autotemcel (Lenti-D, Skysona), its marketed gene therapy for cerebral adrenoleukodystrophy, and 19 patients have started on betibeglogene autotemcel (beti-cel, Zynteglo), its marketed gene therapy for transfusion dependent thalassemia (TDT). As such, bluebird bio has reported 23 total cell collections for SCD/TDT gene therapies lovo-cel and beti-cel. The company expects that patient uptake of the 3 aforementioned therapies will continue to increase, with 85 patient starts expected across the therapies by the end of the year.

“We are seeing clear evidence that our commercial launch is accelerating, with over 20 cell collections completed in SCD and TDT to date in 2024, and more than 40 additional patients already scheduled to initiate the treatment journey for a bluebird gene therapy by the end of this year,” Andrew Obenshain, MBA, the chief executive officer of bluebird bio, said in a statement.

 “We are further encouraged by the commitment to provide patient access across both commercial and government payers, most recently conveyed through multiple positive Medicaid decisions and the growing number of published coverage policies for Lyfgenia, and we expect approximately 85 patient starts across our portfolio this year.”

Notably, unlike lovo-cel, exa-cel is indicated for both SCD and TDT. Since Vertex has not clarified the breakdown of patients treated with exa-cel for each disease, direct comparison is difficult. The approval in TDT came slightly later, with 

“Vertex delivered another strong quarter of revenue growth coupled with outstanding execution across the business, and we are increasing our full year product revenue guidance,” Reshma Kewalramani, MD, the chief executive officer and president of Vertex, said in an August 1, 2024, statement.

 “Our focus for the second half of the year remains on commercial execution in cystic fibrosis and the global launch of Casgevy, readying for the upcoming potential launches of the vanzacaftor triple in cystic fibrosis and suzetrigine in acute pain, while rapidly advancing a robust pipeline that is poised to deliver value for patients and shareholders for the long term.”

Beyond gene therapy for SCD and TDT, uptake of 

hemophilia gene therapies has also been slow

. Although BioMarin’s valoctocogene roxaparvovec (val-rox, marketed as Roctavian) was approved in June 2023, the first patient outside of clinical trials 

 until December 2023, at the Center for Inherited Bleeding Disorders (CIBD) in California.

 Just this month, BioMarin announced that 

 with regard to val-rox, with the company now mainly focusing on distributing the gene therapy in the United States, Germany, and Italy, the 3 countries in which it has been approved for use by relevant regulatory authorities and is reimbursed.

 UniQure and CSL Behring’s hemophilia B gene therapy, etranacogene dezaparvovec (marketed as Hemgenix), which was 

, has also been slow to be embraced by patients.

“We haven't seen a lot of patients dosed yet,” Steven W. Pipe, MD, a professor of pediatric hematology/oncology at CS Mott Children’s Hospital, told 

 regarding Hemegenix earlier in 2024. “And I don't think that’s related to either the enthusiasm of the clinicians or the patients, but really just the mechanics of how to deliver this in the clinical space, as opposed to the research trials... We've seen that a lot of the hemophilia treatment center sites have got their components together, their infrastructure and personnel so that they can actually start delivering this in the commercial setting. And so, I'm really looking forward to seeing this making a difference in patients' lives in a real world setting.”

REFERENCES
1. bluebird bio reports second quarter 2024 results and highlights operational progress and 2024 guidance. News release. bluebird bio, Inc. August 14, 2024. Accessed August 15, 2024. https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-reports-second-quarter-2024-results-and-highlights
2. Stock dive for bluebird as sickle cell gene therapy lags behind Vertex rival. News article. Anna Bratulic. FirstWord Pharma. August 14, 2024. Accessed August 15, 2024. https://firstwordpharma.com/story/5885598
3. Vertex announces US FDA approval of CASGEVY™ (exagamglogene autotemcel) for the Treatment of Transfusion-Dependent Beta Thalassemia. News release. Vertex Pharmaceuticals Incorporated. January 16, 2024. Accessed August 15, 2024. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-us-fda-approval-casgevytm-exagamglogene
4. Vertex reports second quarter 2024 financial results. News release. Vertex Pharmaceuticals Incorporated. August 1, 2024. Accessed August 15, 2024. https://investors.vrtx.com/news-releases/news-release-details/vertex-reports-second-quarter-2024-financial-results
5. Center for Inherited Blood Disorders Administers Country's First Gene Therapy Infusion to Treat Hemophilia A. News release. Center for Inherited Blood Disorders. January 11, 2024. Accessed August 15, 2024. https://firstwordpharma.com/story/5817834?from=article
6. BioMarin Announces Updated Strategy for ROCTAVIAN® to Focus on U.S., Germany and Ital. News release. BioMarin Pharmaceutical Inc. August 5, 2024. Accessed August 15, 2024. https://investors.biomarin.com/news/news-details/2024/BioMarin-Announces-Updated-Strategy-for-ROCTAVIAN-to-Focus-on-U.S.-Germany-and-Italy/default.aspx
7. FDA approves first gene therapy to treat adults with hemophilia B. News release. FDA. November 22, 2022. Accessed August 15, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treat-adults-hemophilia-b

bluebird bio has reported 23 total cell collections for SCD and TDT gene therapies lovo-cel and beti-cel and Vertex Pharmaceuticals has reported approximately 20 cell collections for SCD/TDT gene therapy exa-cel.

Topic

Uptake of Nononcology Gene Therapy Remains Slow in Hematology

(arsa-cel, OTL-200; Orchard Therapeutics) is a gene-edited cell therapy designed to restore arylsulfatase A (ARSA) enzyme activity in children with presymptomatic (PS) late infantile (LI), PS early juvenile (EJ), or early symptomatic (ES) early juvenile (EJ) metachromatic leukodystrophy (MLD).

 arsa-cel under the name Lenmeldy to become the first gene therapy for children with MLD to be approved in the United States, following its approval in the European Union, UK, Iceland, Switzerland, Liechtenstein and Norway under the name Libmeldy.1 Orchard Therapeutics previously announced that the FDA had accepted the biologics license application with 

The FDA’s decision was based on data from patients treated with arsa-cel across 2 clinical trials (NCT01560182; NCT03392987) and additional patients treated in expanded access frameworks. These patients had follow-up times ranging from 0.64 years to 12.19 years (median, 6.76).

“Metachromatic leukodystrophy, is a really important unmet need in the pediatric community. So, this is a disease that's rare, it affects about one in 40,000 children. And up until recently, we have had no curative treatment option for this,” Madeleine Powys, MBBS, Staff Specialist, Blood Transplant and Cell Therapies, The Children's Hospital at Westmead, told 

. "Autologous hematopoietic stem cell gene therapy has offered really promising new hope for these patients.”

Madeleine Powys, MBBS, on Lessons Learned With Libmeldy

Arsa-cel is currently being evaluated in 6 participants enrolled in a phase 3 clinical trial (NCT04283227). The trial enrolled participants with documented biochemical and molecular diagnosis of MLD, including low ARSA activity and identification of 2 disease-causing ARSA alleles, with novel mutations analyzed and excluded as common polymorphisms, alongside specific genotype criteria. Symptomatic individuals must have onset between 7 and 17 years of age, or pre-symptomatic participants must be less than 17 years at treatment initiation and have a sibling with late-juvenile MLD variant, along with normal cognitive and motor function, with seizures or disease signs revealed by instrumental evaluations not being exclusionary if present alone, and compliance with contraceptive use requirements if applicable, with signed informed consent or assent provided by the participant or guardian.

The exclusion criteria for the study include documented HIV infection, malignant neoplasia except localized skin cancer or hereditary cancer syndrome unless successfully treated with no recurrence, myelodysplasia, acute myeloid leukemia, or serious hematological disorders, current enrollment in other interventional trials, prior allogeneic HSPC gene therapy or gene therapy, symptomatic herpes zoster unresponsive to treatment, active tuberculosis unless on antibiotic prophylaxis, acute or chronic stable Hepatitis B or positive Hepatitis C RNA test result unless specific conditions are met, end-organ dysfunction, severe infection not responsive to treatment, or other severe diseases deemed inappropriate for the study by the investigator. Additionally, testing for other transmissible infectious agents may be considered, and participants with elevated liver enzymes or bilirubin may be included after discussion and agreement with the medical monitor.

The study’s primary measures involve assessing the OTpbmsL-200 Arylsulfatase A (ARSA) activity levels in cerebrospinal fluid (CSF) and the neuronal metabolite ratio of N-acetyl-aspartate (NAA) to creatine (Cr) in white matter brain regions, both evaluated at 24 months post-treatment, with changes from baseline being monitored.

Secondary measures involve evaluating changes in ARSA activity levels in CSF and neuronal metabolite ratio in white matter brain regions, assessing ARSA levels in peripheral blood mononuclear cells (PBMCs) and specific subtypes, comparing neuronal metabolite ratios to baseline, siblings, or untreated controls, determining engraftment through lentiviral positivity in bone marrow progenitors and vector copy number in BM cells and PBMCs, assessing severity scale for brain MRI, neurocognitive function, full neurological clinical examination, gross motor function classification, nerve conduction velocity, Vineland Adaptive Behavior Scale, and monitoring conditioning regimen and non-conditioning-related adverse events up to 8 years post gene therapy, along with hematological reconstitution, infusion-related reactions, immune response, abnormal clonal proliferation, replication-competent lentivirus, and integration site analysis findings over time.

, held February 4-9, in San Diego, California, by Vera Gallo, MD, staff pediatrician, San Raffaele Telethon Institute for Gene Therapy. The data were from 5 patients with LJ MLD that had follow-up ranging from 3.2 to 21.3 months (median, 17.3). At the time of treatment, 3 patients had PS MLD and 2 had ES MLD. The group included a 2.7-year-old girl (PS), a 9.9-year-old boy (ES), a 15.2-year-old boy (PS), a 6.6-year-old girl (PS), and 10.9-year-old boy (ES) as of the December 2023 cutoff date.

"This represents of course, the proof of principle that gene therapy with ex- vivo lentiviral gene therapy into stem cells can correct a lysosomal storage disorder (LSD)... and could be applicable to other LSDS. So we're working on new diseases to bring this approach of enzyme correction also to other LSDs," investigator Alessandro Aiuti, MD, PhD, deputy director, clinical research, and head, Clinical Research Unit, San Raffaele Telethon Institute for gene therapy, and Group leader, Pathogenesis and therapy, primary immunodeficiencies unit, and full professor, Università Vita Salute San Raffaele, and chief of clinic, Pediatric Immunohematology Unit, San Raffaele, told 

Data from these participants showed that they all had normal hematological reconstitution and engraftment that was consistent with arsa-cel outcomes seen in patients with early-onset MLD who have been treated in other settings. Time to neutrophil engraftment ranged from 26 to 42 days (median, 33) posttreatment and time to platelet engraftment ranged from 25 to 46 days (median, 26) posttreatment. ARSA activity reached supranormal levels in the PBMCs and in CD15+ cells and increased to normal levels in the CSF in 3 patients for whom central nervous system pharmacodynamic efficacy measures were available.At 90 days after administration of arsa-cel transduced bone marrow progenitors made up between 23.81% to 81.25% of bone marrow progenitors. At this time point, the PBMCs showed a median vector copy number (VCN) of 0.49 copies/cell and the CD15+ cells showed a median VCN of 0.82 copies/cell.

In terms of safety, there were no serious adverse events (SAEs) deemed potentially related to arsa-cel. One nonserious AE deemed potentially related to the therapy, a case of erythematous rash, occurred in 1 patient. No SAEs deemed potentially related to the Busulfan conditioning regimen occurred; although cases of febrile neutropenia, cytopenia, and stomatitis were deemed to have potential relation to the regimen. An SAE of upper respiratory tract infection occurred in 1 patient. One patient with prolonged thrombocytopenia who had previously experienced treatment-failure with allogeneic transplant in the form of autologous reconstitution was administered thrombopoietin receptor agonist therapy for 5 months. No multilineage engraftment of transduced cells or malignancy occurred and there was no indication of clonal expansion or replication competent lentivirus.

1. FDA Approves First Gene Therapy for Children with Metachromatic Leukodystrophy. News release. Orchard Therapeutics. March 18, 2024. Accessed March 18, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-children-metachromatic-leukodystroph
2. Orchard Therapeutics announces acceptance of biologics license application for OTL-200 in MLD and receives priority review. News release. Orchard Therapeutics. September 18, 2023. Accessed September 18, 2023. https://ir.orchard-tx.com/news-releases/news-release-details/orchard-therapeutics-announces-acceptance-biologics-license
3. Fumagalli F, Calbi V, De Mattia F, et al. Long-term clinical outcomes of atidarsageneautotemcel (autologous hematopoietic stem cell gene therapy) preserves cognitive and motor development in early-onset metachromatic leukodystrophy with up to 12 years follow-up. Presented at: WORLDSymposium, held February 4-9, in San Diego, California. Poster #92
4. Gallo V, Calbi V, De Mattia F, et al. Lentiviral hematopoietic stem cell gene therapy (atidarsageneautotemcel) for late juvenile metachromatic leukodystrophy (MLD). Presented at: WORLDSymposium, held February 4-9, in San Diego, California. Poster #96

The gene-edited cell therapy has been approved as Lenmeldy by the FDA. 

Phase 3 Trial Seeks to Continue Supporting Arsa-Cel Gene Therapy for MLD 

This is the second part of an interview with Sven Moller-Tank, PhD. For the first part, 

the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting

, held May 13 to 17, 2025, in New Orleans, LA, Sven Moller-Tank, PhD, a senior director at Regeneron, 

discussed the company's poster presentations at the conference.

 Following up on this, CGTLive additionally asked him about future plans for the company's gene therapy efforts.

Moller-Tank pointed out that the company has pushed forward its unique approach to adeno-associated virus (AAV) targeting in the context of skeletal muscle, the central nervous system (CNS), and the peripheral nervous system, but that it plans to eventually expand beyond those areas. In addition, he spoke about his thoughts on current trends in the field of gene therapy in general.

: Are there any future plans for Regeneron that you can discuss?

 My primary interest is in the targeting component. We're doing a lot of cool stuff outside of that, but I'm going to focus on the targeting. We're continuing to advance our platforms for targeting, again, the skeletal muscle, the CNS, and the peripheral nervous system, and we want to push that to a state where they're ready to go into the clinic. But also we're interested in targeting other tissues. Our entry point was muscle and CNS. We recently expanded to the peripheral nervous system, and we want to expand beyond that, where there are plenty of additional therapeutic opportunities.

Is there anything you want to add about Regeneron's work?

The only other thing is that we're really interested in combining the targeting that we've been developing for AAV, with all sorts of other modalities. So again, siRNA, lipid nanoparticles, these sorts of things. We've had initial success with our AAV, and we think there are great opportunities applying it to other modalities.

Taking a broader view, are there any trends in the industry and/or at ASGCT this year that you are paying close attention to?

Overall, the field in general has realized that gene therapy is extremely challenging and that a lot of the very early promise has been more difficult to deliver on than perhaps we had initially envisioned. But there's a lot of great work that's being done to address the current challenges. In particular, something that we've always emphasized is the need to detarget from the liver. I think the field in general has realized that that's important because of the toxicities associated with delivery to the liver or the peripheral nervous system. You see more and more that companies, especially in their capsid engineering efforts, are emphasizing more and more that this detargeting is an essential component of developing their next generation capsids.

This transcript has been edited for clarity.

Click here to view more coverage of the 2025 ASGCT Annual Meeting.

Sven Moller-Tank, PhD, a senior director at Regeneron, also discussed his thoughts on trends in the gene therapy field in general.

Regeneron’s Future Plans for Its AAV Targeting Approach

The FDA has accepted Atara Biotherapeutics' resubmission of a biologics license application (BLA) for allogeneic Epstein-Barr virus (EBV)–specific T-cell immunotherapy tabelecleucel (tab-cel; Ebvallo), which is intended to treat patients 2 years or older with EBV-positive posttransplant lymphoproliferative disease (EBV+ PTLD) who have received at least 1 prior therapy.

Notably, the BLA resubmission was accepted with priority review and the Prescription Drug User Fee Act (PDUFA) target action date has been set for January 10, 2026. Atara pointed out that as of now there are no therapies approved by the FDA for the aforementioned treatment setting.

“The acceptance of the tab-cel resubmission moves us 1 step closer towards making this first-of-its-kind treatment available to patients in the United States,” Cokey Nguyen, PhD, the president and chief executive officer of Atara, said in a statement.

 “We continue to work closely with the Pierre Fabre Pharmaceuticals team to help prepare for the potential launch in the US.”

Atara previously submitted a BLA for tab-cel to the FDA in May 2024, but was 

 The CRL was related to issues with a standard prelicense inspection of a third-party manufacturer for tab-cel rather than to any concerns regarding the efficacy and safety data contained within the BLA. The manufacturing process itself was not implicated, and the FDA did not request additional clinical trials for tab-cel.

“We are working closely with our partner Pierre Fabre Laboratories, the FDA, and the third-party manufacturer to address the feedback to support marketing approval for Ebvallo,” Nguyen said in a January 2025 statement.

 “Once the third-party manufacturer good manufacturing practice (GMP) compliance issues have been adequately addressed, we will file for a resubmission.... Atara and its partner Pierre Fabre remain confident in the potential of Ebvallo and are committed to bringing this potential first-in-class medicine to United States patients with EBV+ PTLD who have limited treatment options and significant unmet need.”

The BLA is supported by data from the pivotal phase 3 ALLELE clinical trial (NCT03394365) and other studies that cumulatively include greater than 430 patients with multiple diseases. Notably, a 48.8% objective response rate was observed in ALLELE (

 < .0001) in the most up-to-date data, and according to Atara, the safety profile of tab-cel in the trial was favorable and in line with earlier analyses.

Tab-cel is approved in the European Union, the United Kingdom, and Switzerland for the treatment of relapsed/refractory EBV+ PTLD in patients aged 2 years and older who have received at least 1 prior therapy.

 In January 2025, Atara stated that a manufacturing facility located in Thousand Oaks, California, operated by FUJIFILM Diosynth Biotechnologies, a separate third-party manufacturer from the one identified in the aforementioned CRL, had recently gained approval from the European Medicines Agency to manufacture tab-cel.

 Tab-cel has previously received FDA breakthrough therapy designation for rituximab-refractory EBV-associated lymphoproliferative disease and FDA orphan drug designation for EBV-positive post-transplant lymphoproliferative disorders.

Atara is not the only company targeting EBV-associated conditions with cell therapy.

 Biosyngen is currently developing chimeric antigen receptor T-cell therapy BRG01 for EBV-positive relapsed/metastatic nasopharyngeal carcinoma. In August 2024, BRG01 was 

 for a pivotal phase 2 clinical trial in that indication, a decision that was preceded by the Center for Drug Evaluation of China’s National Medical Products Administration 

 for a phase 2 pivotal clinical trial for BRG01 in China.

REFERENCES
1. Atara Biotherapeutics announces U.S. FDA acceptance and priority review of the biologics license application for tabelecleucel (tab-cel®) for the treatment of epstein-barr virus positive post-transplant lymphoproliferative disease. News release. Atara Biotherapeutics, Inc. July 24, 2025. Accessed July 31, 2025. https://investors.atarabio.com/news-events/press-releases/detail/376/atara-biotherapeutics-announces-u-s-fda-acceptance-and
2. Atara Biotherapeutics Submits Tabelecleucel (Tab-cel) Biologics License Application for Treatment of Epstein-Barr Virus Positive Post-Transplant Lymphoproliferative Disease with U.S. FDA. News release. Atara Biotherapeutics. May 20, 2024. Accessed July 31, 2025. https://www.businesswire.com/news/home/20240520985176/en/Atara-Biotherapeutics-Submits-Tabelecleucel-Tab-cel%C2%AE-Biologics-License-Application-for-Treatment-of-Epstein-Barr-Virus-Positive-Post-Transplant-Lymphoproliferative-Disease-with-U.S.-FDA
3. Atara Biotherapeutics provides regulatory and business update on EBVALLO (tabelecleucel). News release. Atara Biotherapeutics Inc. January 16, 2025. Accessed July 31, 2025. https://investors.atarabio.com/news-events/press-releases/detail/367/atara-biotherapeutics-provides-regulatory-and-business
4. Biosyngen’s BRG01 receives FDA approval for phase II clinical trial. News release. Biosyngen. August 12, 2024. Accessed July 31, 2025. https://www.biosyngen.com/index.php/Classification/38.html
5. Biosyngen’s BRG01 enters phase II clinical trial, A first-in-kind autologous EBV-specific CAR-T therapy for solid tumors on recurrent/metastatic nasopharyngeal carcinoma. News release. Biosyngen. July 16, 2024. Accessed July 31, 2025. https://firstwordpharma.com/story/5876299

Notably, the BLA resubmission was accepted with priority review and the PDUFA target action date has been set for January 10, 2026.

FDA Accepts Atara Biotherapeutics’ Resubmission of BLA for Tabelecleucel

The FDA has recommended that Sarepta Therapeutics remove its voluntary hold on United States shipments of Duchenne muscular dystrophy (DMD) gene therapy delandistrogene moxeparvovec-rokl (marketed as Elevidys) for patients who are ambulatory.

In a press release announcing the recommendation, the FDA also stated that it has concluded its investigation of 

 who was treated with Elevidys in Brazil and died on June 7, 2025.

 The agency stated that it has deemed the boy’s death was not related to the Elevidys product.

Although the hold on shipments for Elevidys was voluntary, the FDA had informally requested that Sarepta suspend all shipments of the gene therapy product earlier in July.

 Initially, the company made a public statement that it would not be complying with the request, acknowledging that it had previously paused shipments to patients who are nonambulatory, but would continue to ship the product to patients who are ambulatory. The company justified its decision on the basis of a “comprehensive scientific interpretation of the data” that did not indicate any new or changed safety signals for Elevidys in ambulant patients.

“Last week, at the suggestion of FDA, Sarepta made the difficult decision to pause shipments of Elevidys to provide the FDA with an opportunity to complete a review of available safety information,” Doug Ingram, JD, the president and chief executive officer of Sarepta, said in the statement.

 “We are very pleased that FDA chose to rapidly and comprehensively complete that review and to recommend that we remove our voluntary pause and resume shipment of Elevidys for ambulatory patients. The FDA’s swift review evinces a commitment to the Duchenne population, a commitment shared by Sarepta. We look forward to working collaboratively with the FDA to complete the safety label update for Elevidys and to discussing the approach to risk-mitigation for nonambulatory patients, who remain on pause pending the outcome of those discussions.”

The previous voluntary pause for shipments of Elevidys to patients who are nonambulant, which remains in effect, 

 2 nonambulant patients who were treated with Elevidys died in separate incidents earlier this year.

 Both of these patients’ deaths were attributed to acute liver failure (ALF).

“The FDA will continue to work with the sponsor regarding nonambulatory patients, which remains subject to a voluntary hold, following 2 deaths,” the FDA wrote in its press release recommending the hold for ambulatory patients be lifted.

 “The patient community is an important voice, and the FDA will continue to listen to and respond to thoughts from the community impacted by DMD.”

In addition to the deaths of patients treated with Elevidys, a 51-year-old patient treated with Sarepta’s investigational gene therapy SRP-9004 for nonambulant limb-girdle muscular dystrophy (LGMD) type 2D/R3, which uses the same AAVrh74 serotype as Elevidys, also recently died after receiving the product in a phase 1 clinical trial (DISCOVERY; NCT01976091).

 According to the FDA, this death also appeared to be related to ALF.

 Notably, after this death was announced, the FDA 

revoked the platform technology designation

 it had previously granted to Sarepta for the AAVrh74 viral vector and placed clinical holds on all trials currently evaluating SRP-9004 and bidridistrogene xeboparvovec (also known as SRP-9003), which is an investigational gene therapy product in development by Sarepta for LGMD type 2E (also known as β-sarcoglycanopathy) that also uses the AAVrh74 vector.

REFERENCES
1. FDA recommends removal of voluntary hold for Elevidys for ambulatory patients. News release. FDA. July 28, 2025. Accessed July 30, 2025. https://www.fda.gov/news-events/press-announcements/fda-recommends-removal-voluntary-hold-elevidys-ambulatory-patients
2. FDA investigating death of 8-year-old boy who received Elevidys. News release. FDA. July 25, 2025. Accessed July 30, 2025. https://www.fda.gov/news-events/press-announcements/fda-investigating-death-8-year-old-boy-who-received-elevidys
3. Sarepta Therapeutics provides clarifying statement on Elevidys. News release. Sarepta Therapeutics, Inc. July 25, 2025. Accessed July 30, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-provides-clarifying-statement-elevidys
4. Sarepta Therapeutics provides statement on Elevidys. News release. Sarepta Therapeutics, Inc. July 18, 2025. Accessed July 30, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-provides-statement-elevidys
5. FDA informs sarepta that it recommends that sarepta remove its pause and resume shipments of ELEVIDYS for ambulatory individuals with duchenne muscular dystrophy. News release. Sarepta Therapeutics, Inc. July 28, 2025. Accessed July 30, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/fda-informs-sarepta-it-recommends-sarepta-remove-its-pause-and
6. Sarepta provides safety update for ELEVIDYS and initiates steps to strengthen safety in non-ambulatory individuals with Duchenne. News release. Sarepta Therapeutics, Inc. June 15, 2025. Accessed July 30, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-provides-safety-update-elevidys-and-initiates-steps?_ga=2.73448155.831031676.1750179906-198354166.1749064502
7. Sarepta Therapeutics shares safetyupdate on Elevidys. News release. Sarepta Therapeutics, Inc. March 18, 2025. Accessed July 30, 2025. https://investorrelations.sarepta.com/static-files/0d505d91-6722-4528-aae0-1e99fcbc37e5
8. Sarepta Therapeutics provides statement on Elevidys. News release. Sarepta Therapeutics Inc. July 18, 2025. Accessed July 30, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-provides-statement-elevidys
9. Philippidis A. StockWatch: Sarepta shares nosedive after LGMD gene therapy patient dies. Genetic Engineering & Biotechnology News. July 20, 2025. Accessed July 30, 2025. https://www.genengnews.com/topics/genome-editing/stockwatch-sarepta-shares-nosedive-after-lgmd-gene-therapy-patient-dies/
10. FDA requests Sarepta Therapeutics suspend distribution of Elevidys and places clinical trials on hold for multiple gene therapy products following 3 deaths. News release. FDA. July 18, 2025. Accessed July 30, 2025. https://www.fda.gov/news-events/press-announcements/fda-requests-sarepta-therapeutics-suspend-distribution-elevidys-and-places-clinical-trials-hold
11. U.S. FDA grants platform technology designation to the viral vector used in SRP-9003, Sarepta’s investigational gene therapy for the treatment of limb girdle muscular dystrophy type 2E/R4. News release. Sarepta Therapeutics Inc. June 4, 2025. Accessed July 30, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/us-fda-grants-platform-technology-designation-viral-vector-used

The FDA also stated that it has concluded its investigation of the death an 8-year-old boy who was treated with Elevidys in Brazil.

FDA Gives Sarepta Green Light to Restart Shipment of DMD Gene Therapy Elevidys to Patients Who Are Ambulatory

In Episode 5 of ImmunoLogic, Michael T. Lotze, MD, discussed the evolution and future of tumor infiltrating lymphocyte (TIL) therapies.

ImmunoLogic, Episode 5: "Tumor Infiltrating Lymphocytes" With Michael T. Lotze, MD

We're excited to introduce another episode of the 

an assistant professor of microbiology and the director of the Fraietta Lab at the University of Pennsylvania. Fraietta is often joined by cohost 

 a clinical fellow in oncology (MSTR Program) at the University of Pennsylvania. Our hope is that this show will serve as a critical forum for clinicians, translational researchers, and biotech professionals to explore the evolving landscape of immunotherapy. We're seeking to bridge cutting-edge research with practical applications and delve into how immune-based therapies transition from innovative discoveries to transformative patient care solutions

a professor of surgery, immunology, and bioengineering at the University of Pittsburgh, about his work on tumor infiltrating lymphoctye (TIL) therapy. Fraietta and Lotze covered topics including the history of TIL research, the potential of TIL therapy in different tumor types, Lotze and his colleagues' new reciprocal learning model hypothesis, and concluded with some philosophical reflections on cancer research.

 is tailored for an audience fluent in the language of medicine and biotechnology, offering data-driven insights while maintaining accessibility. This podcast is an essential resource for those driving the future of immunotherapy.

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In episode 5 of ImmunoLogic, Michael T. Lotze, MD, discusses the evolution and future of tumor-infiltrating lymphocyte therapies.

J. L. González-Larriba, MD, PhD

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